The reversibility of micro-vascular complications of diabetes mellitus will be assessed by examination of the effects of islet of Langerhans transplantation into experimentally-induced diabetes in in- bred rats. Studies will include thorough examination of islet function such as glucose tolerance tests and insulin, glucagon, and growth hormone measurements before and after transplantation. The reversibility of renal glomerulosclerosis will be examined in terms of light and electron microscopy, mesangial metabolism of colloidal carbon and disappearance of macromolecules such as serum proteins as studied by fluorescence microscopy. Ophthalmologic studies will include light and electron microscopic examination of the retina as well as application of colloidal carbon techniques to study retinal vessel permeability. The effects of hypertension and uremia upon the progression and reversibility of retinopathy will be examined using renal arterial clipping and nephrectony as appropriate induction for each problem respectively. The latter experiments will attempt to reproduce the clinical situation as it presents with severe retinal involvement with human microvascular complications of diabetes mellitus.